ABSTRACT Osteoarthritis (OA) affects over 30 million US adults: it is one of the most common chronic health conditions and a leading cause of pain and disability among adults. OA is a degenerative disease of the articular joints characterized by focal areas of cartilage fibrillation, articular cartilage hypertrophy, bon changes, and eventual destruction of the articular surface. Current FDA approved treatments for OA mainly relieve pain without slow- ing the progressive degeneration. Other than the regular use of painkillers, few therapeutic options exist. Over 63% of patients with OA are dissatisfied with their current OA therapy and a significant number eventually seek surgery. There is a critical need for new therapeutic strategies to combat OA. The inflammation, cartilage de- generation, and pain associated with OA have all been proposed to be caused by a common factor: the in- creased synthesis of the reactive form of oxygen called superoxide radical anions (SRA) by polymorphonuclear leucocytes and chondrocytes in joints. BG-137 is a small molecule that reduces the synthesis of SRA. Using guinea pigs with natural OA, we will use BG-137 as a tool to reduce the amount of SRA synthesized by their joint cells to levels closer to those observed in healthy animals without OA. We will evaluate whether doing so prevents the symptoms of OA and the rate at which OA progresses. This work will determine the extent to which reducing levels of SRA can be used as a therapeutic strategy to treat OA.